Quadrupole mass filters have been widely used for decades for routine mass spectrometric analysis of a variety of substances, including small molecules such as pharmaceutical agents and their metabolites, as well as large biomolecules such as peptides and proteins. More recently, two-dimensional radial-ejection ion traps (also known as “linear ion traps”) have achieved widespread use (see, e.g., Schwartz et al., “A Two-Dimensional Quadrupole Ion Trap Mass Spectrometer”, J. Am. Soc. Mass Spectrometry, 13: 659-669 (2002)). Generally described, such quadrupolar mass-analysis devices are grossly similar in structure and consist of four elongated electrodes, each electrode having a hyperbolic-shaped surface, arranged in two electrode pairs aligned with and opposed across the centerline midway between each electrode pair.
In both linear ion traps and quadrupole mass filters, there are four parallel rods, each spaced from a central axis, and typically shaped with hyperbolic or round rod profiles. Generally, the long dimension of the rods defines a Z-axis of a Cartesian coordinate system. Opposite phases of an RF voltage are applied between the rods separated in the X dimension, versus those separated in the Y dimension. This applied RF voltage affects the movement of ions in the X and Y dimensions, including the containment of the ions within the device. For linear ion trap operation, an axial containment field is added either through lens elements, or rod segments, to which an additional DC voltage can be applied to contain ions along the Z dimension.
In operation of quadrupole mass filter (QMF) devices, ions comprising a range of mass-to-charge (m/z) ratios are introduced into an entrance end of the apparatus along trajectories that are roughly parallel to the centerline. By properly choosing the magnitude of DC and RF voltages applied to the rods, the range of ions that pass completely through the apparatus can be restricted to only a desired narrow m/z range. The ions so transmitted may then be detected by a detector aligned so as to intercept ions that pass entirely through the apparatus, from one end to another. The detector generates a signal representative of the number of transmitted ions. The detector signals are conveyed to a data and control system for processing and generation of a mass spectrum.
In one form of linear ion trap device used for mass analysis, at least one of the electrodes of an electrode pair is adapted with an aperture (slot) extending through the thickness of the electrode or electrodes in order to permit ejected ions to travel through the aperture to an adjacently located detector. Ions are radially or transversely confined within the ion trap interior by applying opposite phases of a radio-frequency (RF) voltage to the electrode pairs, and may be axially or longitudinally confined by applying appropriate DC offsets to end sections or lenses located axially outward of the electrodes or central sections thereof. To perform an analytical scan, typically a dipole resonant excitation voltage is applied across the electrodes of the apertured electrode pair (often referred to as the X-electrodes because they are aligned with the X-axis of a Cartesian coordinate system, which is oriented such that X and Y are the radial axes of the trap and Z is the longitudinal axis extending along the trap centerline) while the amplitude of the RF voltage is ramped. This operation causes the trapped ions to come into resonance with the applied excitation voltage in order of their m/z ratios (m/z's). The resonantly excited ions develop unstable trajectories and are ejected from the trap through the aperture(s) of the X-electrodes to the detectors.
Each class of quadrupole mass analyzer—either quadrupole mass filters or linear ion traps—is associated with its own unique advantages. Ion traps are known for their high sensitivity for full-scan mass analysis, the ability to do iterated fragmentation and analysis (MSn) experiments, and their high scan speed. Quadrupole mass filters are known for their ultimate sensitivity and limits of detection for targeted compound analysis and quantization. This disclosure relates to creating a single device that can act as both a linear ion trap and a quadrupole mass filter and thus can achieve the combination of performance characteristics, while saving the cost and complexity of having two separate devices within a mass spectrometer instrument. This creates a versatile device which has the ideal qualitative capabilities of ion traps while additionally maintaining the quantitative performance aspects of a QMF.
It is known that the slots necessary for linear ion trap operation cause a perturbation to the electric field and distort it away from the pure linear field. Various ways have been proposed to compensate for the deleterious performance effects of apertures put into the electrodes of ion trap apparatuses, including both three-dimensional (3D) ion traps (e.g., Paul traps) as well as linear ion traps. In some currently-available commercial linear ion trap systems, compensation for the effects of the slots is accomplished by stretching the electrode spacing outward from the theoretical optimum spacing for non-slotted hyperbolic rods. Essentially, this method of compensation introduces primarily positive octopolar and dodecapolar higher order (non-linear) fields, which compensates for the negative field distortions created by the slots. However, this method of compensation can not yield complete cancellation of the non-linear higher order fields. As a result, in the current implementation, often, some over compensation occurs, which still leaves some higher order fields for effective performance. Although the apparatus that is compensated in this fashion can operate well as an ion trap mass analyzer, it is desirable, for QMF operation, to be able to generate an RF field that is, essentially, as pure a quadrupole potential (linear field) as possible. Moreover, such compensation mechanisms are not readily adjustable. Preferably, any field distortion compensation mechanism should be adjustable in a fashion so as to be able to compensate for the effects of the ejection slot (so as to achieve optimum ion trap performance) while also being able to make the appropriate field corrections for operation in QMF mode, since these two modes of operation may have different field compensation requirements. The adjustment mechanisms could be employed both in real-time during instrument operation and also during instrument calibration so as to correct for distortions introduced by manufacturing mechanical defects.
U.S. Pat. No. 8,415,617 teaches one approach to achieving functionality as both an ion trap and a QMF by requiring the slots to be configured such that a four-fold symmetry is achieved, thereby resulting in a negligible octopole field component and a predominant dodecapole or icosapolar field distortion. Although this symmetrical configuration significantly reduces the level of field distortion, the residual non-linear fields caused by the slots can still have a deleterious effect on QMF performance. To allow the same structure to also operate as a more-ideal quadrupole mass filter (QMF) theoretically requires even further correction, requiring a more pure linear (quadrupolar) electric field, with near-complete cancellation of all non-linear fields.
The goal of providing the highest level of field correction, along with operationally-adjustable compensation leads to compensation methods which are more local to the slots, versus a global adjustment like stretching of the rod spacing as described above, or changing of the hyperbolic asymptote angles as is employed in some three-dimensional ion trap devices. One such approach that has been considered with regard to 3D ion traps is to put local protrusions, or bumps, adjacent to the slots. Such an approach has been described, for example, in United States pre-grant publication No. 2004/0195504 A1 and U.S. Pat. No. 6,087,658 in which local electrode bumps are used for field tailoring in order to optimize 3D ion trap performance. Although this approach shows some promise, it is limited in regard to the present objectives in that it does not readily allow adjustment of the field compensation when different compensations are needed for ion trap versus QMF mode. This approach is further limited in that it does not allow for general field-distortion correction, including correction of distortions introduced by manufacturing mechanical defects, for any given device.
U.S. Pat. No. 8,415,617 teaches using “shim” electrodes to achieve correction of field distortions due to the holes in the endcap electrodes of a 3D ion trap. This concept consists of using an additional electrode which is inserted into the aperture, to which a voltage can be applied. This voltage can compensate for the potential fall off caused by the existence of the hole in the endcap electrode, thereby flattening the equipotential contour to produce a more pure quadrupolar potential and associated linear field. The present inventor has realized that a similar concept may be extended to a linear ion trap, thereby allowing the same apparatus to also be used as a QMF.